A mixed bag of epidemiologic studies alternatively hold up and knock down the promise that widely prescribed cholesterol-lowering statin drugs might offer some protection against Alzheimer disease progression (see ARF related news story). Laboratory studies showing that cholesterol or statins both can influence the production of Aβ (ARF related news story and ARF news story) have further piqued interest in prospective, controlled studies of statins for treating AD. Now, preliminary results of a small, placebo-controlled clinical trial using atorvastatin in people with mild to moderate AD should further encourage statin fans. The study, led by Larry Sparks at the Sun Health Research Institution in Sun City, Arizona, and just published in the May Archives of Neurology, produced significantly better scores on several measures of cognitive function in atorvastatin-treated patients compared to the placebo group. If these preliminary results hold up in larger, multicenter trials, atorvastatin may prove to be an effective therapy for AD, according to the authors, who report two larger studies are ongoing.
The pilot trial enrolled 67 people who took atorvastatin or placebo daily for a year. The participants were evaluated at baseline and then every 3 months with standard measures of cognitive function. The atorvastatin group did better in tests of cognitive function (ADAS-cog) and depression. At 12 months, none of the differences were significant, but the numbers indicated a trend toward higher scores on ADAS-cog, and two other clinical scales. As expected, the treated group had significantly lowered blood cholesterol.
Other newly published clinical data, this from the interrupted testing of Elan’s Aβ vaccine, slightly extends previously reported results. The treatment phase of the trial was stopped early when several participants developed encephalitis, but follow-up continued on the 300-odd patients who had already received one, two, or three doses of the vaccine. Two papers in the May 10 print edition of Neurology recap the trial results which were presented last summer at the 9th International Conference on Alzheimer’s Disease and Related Disorders (see ARF related news story). One paper by Nick Fox at the Institute of Neurology in London and colleagues outlines the surprising and as yet unexplained results of MRI measurements showing that patients in the treatment group who responded to vaccine with antibody production experienced a decrease in brain size (see additional coverage from Sorrento). A second paper from Sid Gilman of the University of Michigan at Ann Arbor and his coinvestigators found no significant differences when they compared the vaccine responders to nonresponders on a number of cognitive function tests. A battery of nine neuropsychological tests revealed only one significant difference, on one of the Wechsler memory tests. But analysis of scores across the entire series revealed significantly better composite scores for the responders compared to placebo. This result, and the observation that tau protein levels were decreased in antibody responders compared to the placebo group, suggests that the vaccine approach may prove useful, if toxicity issues can be addressed. The authors speculate that the encephalitis that halted the trials, an adverse event that was not seen in any of the preclinical animal models or safety tests, might have resulted from a change in formulation of the vaccine during a phase I trial. If so, the prospects for taming the vaccine to elicit the beneficial effects of amyloid removal without the immunological side effects would appear to be bright.—Pat McCaffrey
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- Sparks DL, Sabbagh MN, Connor DJ, Lopez J, Launer LJ, Browne P, Wasser D, Johnson-Traver S, Lochhead J, Ziolwolski C. Atorvastatin for the treatment of mild to moderate Alzheimer disease: preliminary results. Arch Neurol. 2005 May;62(5):753-7. PubMed.
- Gilman S, Koller M, Black RS, Jenkins L, Griffith SG, Fox NC, Eisner L, Kirby L, Rovira MB, Forette F, Orgogozo JM, . Clinical effects of Abeta immunization (AN1792) in patients with AD in an interrupted trial. Neurology. 2005 May 10;64(9):1553-62. PubMed.
- Fox NC, Black RS, Gilman S, Rossor MN, Griffith SG, Jenkins L, Koller M. Effects of Abeta immunization (AN1792) on MRI measures of cerebral volume in Alzheimer disease. Neurology. 2005 May 10;64(9):1563-72. PubMed.